In order to test the potential advantages of improved dose distribution (helium) and increased biological effect (neon, carbon), a clinical trial is being conducted to study the therapeutic application of these heavy charged particles in the treatment of human cancers. Fractionated, large field, spread out Bragg peak charged particle radiotherapy treatment techniques are being continually refined together with improved techniques for assessment and compensation of tissue inhomogeneities utilizing CT scanners to obtain tissue densities in the particle beam paths. Several pilot protocols with helium have been instituted, leading so far to one randomized trial: helium ion treatment plus 5-FU versus conventional radiation therapy plus 5-FU. We have also instituted Phase I-II pilot studies with heavier ions such as carbon and neon. Our ultimate goal is to test heavy charged particles against the best available therapy in a randomized trial of selected tumors. Existing cooperative study groups such as the Radiation Therapy Oncology Group and the Northern California Oncology Group are being utilized to facilitate these trials, together with the Bay Area Heavy Ion Assessment.